Information about Military and Civilian Biodefense/Terrorism Countermeasures, vaccines, laws and policies

May 30, 2006

Vaccines: Back on the Front Burner

Europe, Business Weeklyby Kerry Capell

Once a neglected field, vaccine research is taking off due to fear of pandemics. And units such as Novartis' Chiron are where the action is

Compared with glamour drugs designed to battle cholesterol, high blood pressure, and depression, vaccines have long been the poor relations of the pharmaceutical industry. After all, ravages such as smallpox, polio, and measles were long ago cured. But now, thanks to the emergence of avian flu and other new viruses -- plus improved technology and better economics -- vaccines are becoming the global drug industry's next hot sector.

For proof, simply visit the Siena, Italy, labs of biotech Chiron, a unit of drugmaker Novartis (NVS). It was here, tucked between vineyards and farms in the Tuscan hills, that the world's first avian-flu vaccine was developed in 1998. "Back then, no one was interested," recalls Rino Rappuoli, the scientist who led the research. "Now it's a totally different story." With fears that the avian-flu virus sweeping Asia might evolve into a form that could easily jump to humans, governments are calling on vaccine manufacturers to find a solution.

Scientists in Siena have developed a vaccine with an ingredient known as an adjuvant that renders it more effective at low doses. That's a big advantage, given the current capacity constraints among vaccine manufacturers. Moreover, Rappuoli's team is also responsible for what's likely to be Europe's first seasonal flu vaccine produced from cell-based manufacturing. Expected to hit the market later this year, the cell-based vaccine can be produced much faster than conventional types, which require growing flu viruses in millions of chicken eggs.

POOR RELATION NO MORE. Such innovation is one of the main reasons Swiss pharmaceutical giant Novartis (NVS) ponied up $5.4 billion for Chiron in April, 2006. The global vaccine market is worth $10.8 billion today -- less than the nearly $13 billion in sales generated by Pfizer's (PFE) cholesterol-lowering drug Lipitor alone.

But analysts reckon the vaccine market will grow much faster than the market for prescription drugs. "We're in a period where pharmaceutical sales are growing at 5% to 6% a year," says Novartis Chief Executive Daniel Vasella. "In contrast, the vaccine industry is looking at nearly 20% annual growth over the next five years."

It's a dramatic change for a neglected corner of the giant global drug industry. Until recently, vaccines simply weren't a very attractive business. "Pricing was unattractive, margins nonexistent, and there was a constant fear of litigation," Vasella says. From more than 20 players in the 1980s, the field of manufacturers shrank to only five today -- France's Sanofi-Aventis (SNY), Merck (MRK) and Wyeth (WYE) in the U.S., Britain's GlaxoSmithKline (GSK), and Novartis.

PROFIT MACHINES. Today, the vaccine business is undergoing something of a renaissance. That's feeding an explosion of biotech startups targeting opportunities in everything from new methods of delivery to so-called therapeutic vaccines that treat diseases patients already have. In 1989, there were fewer than 10 biotech vaccine companies, but today there are nearly 200. The number of new vaccines in development also has more than tripled over the last decade, to 150 today. "It's proof that the business is waking up and becoming much more interesting," says Joerg Reinhardt, CEO of Novartis' newly-created vaccines and diagnostics business.

Credit a convergence of scientific advances, policy changes, and improved economics. Merck and GlaxoSmithKline paved the way in the late 1980s, when they developed genetically-engineered vaccines for Hepatitis B. Safer and more effective than previous drugs, they commanded premium prices that showed vaccines could be profit machines.

The picture has also improved thanks to tort reform and legislation that reduced liability risks for drugmakers. And the mapping of the human genome has exponentially increased the number of targets for new vaccines.

ESCALATING INFO. Novartis' new meningitis-B vaccine shows how far the industry has come. Scientists had previously managed to develop vaccines for other strains of meningitis, a potentially fatal infection of the nervous system, but the B strain, responsible for 50% of cases worldwide, proved impossible. Chiron's Rappuoli convinced Craig Venter, one of the leaders in the mapping of the human genome and the founder of Maryland's Institute for Genomic Research, to sequence the genome of meninigococcus B.

"In 18 months, we acquired more knowledge to develop new vaccines than in the past 50 years," Rappuoli says. Novartis is furthest ahead in developing a vaccine for meningitis B, and potentially will be the first to market a combination vaccine for meningitis strains for use in infants.

But it's flu vaccines that are expected to drive growth in the immediate future. Novartis is the second-largest flu-vaccine producer, with 11% of the market, well behind Sanofi-Aventis' 58% share. Contamination problems at Chiron's plant in Liverpool forced it to shut down production. Reinhardt, who reckons the problems will be fully resolved in time for next flu season, aims to close the gap.

CLOSING THE GAP. Things are already looking up. On May 4, Novartis was one of a handful of companies awarded multimillion dollar contracts by the U.S. Health & Human Services Dept. to work on cell-based production technologies as part of the government's avian-flu pandemic plan. Reinhardt says the company will use the $221 million contract from the HHS to fund the construction of a new cell-based plant in the U.S. that will supply the American market only.

With potential blockbusters in the pipeline, a new plant in the works, and substantial investment, sales at Novartis' vaccine business could rise from $1 billion to $3.4 billion by 2012, predicts brokerage Bear Stearns. Operating profits over the same period could zoom from $207 million to $1.4 billion.

"The old image of the vaccine business as all hassle no profit couldn't be more wrong," Vasella says. Now, drugmakers can do good and do well at the same time.

May 24, 2006

Anthrax Contract Dispute Could Reverberate Across Biotech Industry

Biotech company VaxGen is seeking recourse against the Department of Health and Human Services (HHS) for changing the terms of its anthrax vaccine contract without providing additional compensation.

VaxGen was awarded the $877.5 million contract under Project BioShield, and is charged with supplying the government with 75 million doses of a second-generation anthrax vaccine.

Although the biotech company was slated to deliver the vaccine as early as the end of this year, HHS ordered additional tests, postponing delivery until at least the end of 2007.

Observers in both industry and the government see the partnership's success as pivotal to encouraging other biotech companies to support future biodefense efforts.

"As precedent, this is a terrible step on the part of the government," said Sharon Seiler, a biotechnology analyst who covers VaxGen at investment bank Punk Ziegel & Company. "This contract is about more than just getting anthrax vaccine. Essentially, the government can move the goal posts any time it wants."

In a statement, HHS described the contract modifications as an "extension of time" and not a change in requirements.

Seiler noted that "it's hard to tell what the truth is," but said it appears the changes relate to tests that had originally been scheduled post-shipment, and are now required prior to delivery. VaxGen does not get paid until after it delivers the doses.

An HHS spokesman declined comment beyond the prepared statement.

"It is incontrovertible that there is a modification," said Lance Ignon, Vaxgen's vice president of corporate affairs. "We can see the rationale behind that --but clearly we should be treated fairly."

VaxGen has proposed a number of options to HHS, such as increasing the value of the contract, Ignon noted.

"These additional data will merely be confirmatory; it won't be new data," he said.

A report from the Government Accountability Office noted that Project BioShield was supposed to set a new standard for accelerated vaccine development.

"Problems with this initial Project BioShield contract could affect the biotechnology industry's response to future government overtures to develop and procure medical countermeasures against the many other biothreat agents still to be addressed," the report stated.

Separately, HHS has expanded its contract with BioPort to purchase an additional five million doses of its BioThrax anthrax vaccine for the Strategic National Stockpile. It has also put out a request for proposals from companies that can develop a third generation vaccine, which would be effective in only one to two doses.

Secret FEMA Plan to Use Pastors as Pacifiers in Preparation For Martial Law

Legit Governmenthttp://www.legitgov.org/index.html#breaking_news

By Paul Joseph Watson

"A Pastor has come forward to blow the whistle on a nationwide FEMA program which is training Pastors and other religious representatives to become secret police enforcers who teach their congregations to 'obey the government' in preparation for a declaration of martial law, property and firearm seizures, and forced relocation... It falls under the umbrella of the NVOAD program... Pastor Revere [pseudonym] outlined the plan to carry out mass vaccination and enforced drugging programs in times of crisis such as a bird flu outbreak. 'In the event of an outbreak or a bio-terrorist attack, there'd be a mass vaccination....they have a program nationwide 'Pills in People's Palm In 48 Hours'," said the Pastor..."

Psychiatric drugs fare favorably when companies pay for studies

USA TodayBy Marilyn Elias

Drug companies fund a growing number of the studies in leading psychiatric journals, and drugs fare much better in these company-funded studies than in trials done independently or by competitors, researchers reported Wednesday. About 57% of published studies were paid for by drug companies in 2002, compared with 25% in 1992, says psychiatrist Igor Galynker of Beth Israel Medical Center in New York City.

His team looked at clinical research in four influential journals: American Journal of Psychiatry, Archives of General Psychiatry, Journal of Clinical Psychiatry and Journal of Clinical Psychopharmacology.

In the report, released at the American Psychiatric Association meeting in Toronto, reviewers did not know who paid for the studies they evaluated, Galynker says. There were favorable outcomes for a medication in about:

. Eight out of 10 studies paid for by the company that makes the drug.

. Five out of 10 studies done with no industry support.

. Three out of 10 studies done by competitors of the firm making the drug.

The findings don't prove the companies are knowingly biasing studies, says co-author Robert Kelly Jr., also with Beth Israel. The report didn't look at the evidence for bias in design of the studies.

As drug companies increasingly fund research that yields favorable outcomes for their drugs, there may be a built-in bias because journals are reluctant to publish studies with negative or inconclusive findings, Galynker says.

In October 2004, the pharmaceutical industry set up a database to allow publication of all studies, positive and negative, says Alan Goldhammer of the Pharmaceutical Research and Manufacturers of America, trade group for the drug companies. "We want to improve transparency," he says.

Because drug studies are very expensive, pharmaceutical companies fund those most likely to have a positive outcome, Goldhammer says. The firms weed out drugs that don't work and consult with the Food and Drug Administration to design trials that will pass muster with the FDA. "We're constantly trying to develop new drugs to treat mental illness," he says.

Posting a negative study on the database is voluntary. "And common sense dictates that the worse the drug does, the less likely you are to volunteer to beat yourself up publicly by sharing that," says Sidney Wolfe of Public Citizen, the Washington-based consumer advocacy group.

"We're seeing a huge tilting in the education of psychiatrists toward the industry point of view on psychiatric drugs," Wolfe says. "And that point of view is, 'Prescribe my drug, it's better.'"

The government should be funding more of this research because public programs, such as Medicare, pay so much for psychiatric drugs, Wolfe says.

May 23, 2006

As the dire predictions of a pandemic mount, skeptics warn of the dangers of overreaction

Houston ChronicleBy TODD ACKERMAN

Some don't buy bird flu threat

For months, the warnings have been relentless: Bird flu could jump species and kill tens of millions of people, a pandemic to rival the 1918 Spanish flu. Economies would collapse and governments risk catastrophe if they don't put together elaborate contingency plans.

Not everyone is convinced, however. A small group of skeptics says the warnings are just a lot of hype, scare talk that does more harm than good to the public health. Such doomsday predictions go well beyond good science and siphon money and attention from more important threats, they say.

"It's a great story, a disease that can wipe out mankind as we know it," says Dr. Gary Butcher, a University of Florida veterinarian specializing in avian diseases. "Fortunately, the facts are contrary to what's being reported. This disease is going to fizzle out, be forgotten in the near future and be replaced by another 'potential worldwide threat.' "

That view may have received a boost last week when the United Nations' chief pandemic flu coordinator confirmed that the flu virus known as H5N1 largely has been contained in the Asian countries where it first hit.

Public health officials were quick to warn it would be premature to declare victory. Dismissive of those who play down the threat, they argue it would be irresponsible not to plan for a worst-case scenario.

H5N1, they note, shares many genetic features with the Spanish flu, according to a research team that reconstructed the horrific 1918 virus - except it's even more lethal. The new virus has killed nearly 57 percent of its 217 confirmed human carriers. The 1918 pandemic paralyzed society, but the resulting 20 million to 50 million deaths represented just 2 percent of those infected.

In addition to common flu symptoms like fever and cough, those infected with the H5N1 virus can develop viral pneumonia or other life-threatening complications within days. The virus, to date, is believed only to have been transmitted to humans through direct contact with diseased birds.

Virus transmission

The most recent reported deaths attributed to H5N1 were those of six Indonesians, five of them in an extended family. The deaths, reported last week, initially were investigated as a "cluster" that health experts feared could mean the virus was mutating into a form more easily passed between humans. World Health Organization investigators have all but ruled out human-to-human transmission, saying the virus likely was caught from infected animals.

It's the idea of easy transmission between humans that brings out the apocalyptic visions. One researcher went so far as to suggest half the world's population could die in such a pandemic. U.S. Secretary of Health & Human Services Michael Leavitt advised Americans to stockpile cans of tuna fish and powdered milk in case of an outbreak. And officials have called for more than 100 million doses of a still-to-be-developed vaccine for the virus to be made available to Americans.

Contrarians such as Butcher say it's all a bit much, considering that some experts doubt the current lethal form of the virus will ever jump to humans They also note that the three pandemics of the last century claimed successively fewer lives. The last, in 1968, killed 34,000 people, fewer than the number who succumb each year to seasonal flu.

Bird flu, they argue, is just the latest in a line of overhyped scares that include anthrax, West Nile virus, smallpox and SARS, which taken together claim a mere fraction of the lives lost every year to, say, pneumonia.

The skeptics warn of the dangers of overreaction, citing 1976's swine flu debacle, when more than 40 million people received a vaccine against a new pig virus that, ultimately, never took hold. The virus killed one person, a military recruit whose speedy death ignited the crash program. But as many as 1,000 people who were inoculated developed a paralyzing nerve condition; 32 died. The public relations nightmare and lawsuits against the government helped drive many drug companies away from making flu vaccines at all.

One reason some remain unconvinced of the new virus's potential transmissibility is because it has infected so few people to date. Since 1998, hundreds of millions of chickens in Asia have been infected with the virus. Millions of people lived with the diseased birds, but, as of last Friday, 217 had become infected. Of those, 123 died.

The high fatality rate also is suspect, according to the naysayers. No one knows how many people in close contact with domesticated birds may have picked up the virus, but never got sick or only showed mild symptoms, and, thus, never reported the disease.

The current flu virus, H5N1, is what is infecting birds. That virus, however, infects humans by lodging deep in the lungs, and, thus, isn't likely to be spread by coughing or sneezing.

The fear among scientists is that the avian flu strain will mix with a human flu, producing a new, easily transmissible virus against which people have no immunities.

"It would be devastating if it gained the ability to spread easily from person to person," said Dr. Wendy Keitel, a molecular virologist at Baylor College of Medicine. "Its fatality rate in humans is unprecedented, as is the extent and severity of the outbreaks in poultry."

Differing views

But Paul Ewald, a professor of evolutionary biology at the University of Louisville, said such pathogens would lose their virulence, a law of natural selection ignored by those who fear the worst-case scenarios.

"Everything we know about evolution says pathogens have to become more mild to keep their host mobile," Ewald said. "If they're so virulent the host can't pass them on, they don't survive."

The exception, he said, occurs in "disease factories" - environments where people immobilized by illness can easily transmit a virulent pathogen to new hosts - which is what happened on World War I's Western Front with the Spanish flu. Hospitals, trains and trenches packed with deathly ill and healthy soldiers facilitated the disease's lethal spread.

Public health officials respond that researchers still don't know exactly what made the Spanish flu so deadly, particularly to the young and healthy. They say they can't afford to do little and hope time proves Ewald's theory correct.

Are grants driving hype?

Some critics see a different "agenda" behind the public concern about bird flu - funding. Butcher says President Bush's $7.1 billion flu pandemic plan means a bonanza of grant money for researchers and the justification of the budgets and existence of agencies such as the U.S. Department of Agriculture and the World Health Organization.

The bait is not taken by many officials most concerned about the bird flu threat. One such, Dr. C.J. Peters, director of biodefense at the University of Texas Medical Branch at Galveston, calls the more vocal skeptics "well-intentioned folks reacting to media hype."

Some mostly just wish the money wasn't being directed so single-mindedly to the new virus. With nearly 150 different strains of flu viruses with the potential to cause a pandemic, New York University School of Medicine internist Dr. Marc Siegel said he'd like to see more effort aimed at general pandemic preparation, such as developing better methods for making vaccines, and less given to panic-inducing rhetoric.

"I'm concerned that the public discussion about bird flu, the new bug du jour, is so weighted with end-of-the-world terms that it's causing a kind of hysteria," said Siegel, author of Bird Flu: Everything You Need to Know About the Next Pandemic. "The greatest problem isn't influenza - it's fear of influenza."

Avoid use of police or army to enforce public heath

Dr. D.A. Henderson, who helped wipe out smallpox around the world, has a piece of advice for governments fighting bird flu -- Don't use the military or police to enforce public health.

Henderson, who likes to describe how he was vaccinated thousands of times against smallpox to demonstrate the immunization's safety to wary villagers, says it is much easier to halt epidemics by winning the trust of community leaders and making use of gossipy schoolchildren.

He is critical of parts of the U.S. national pandemic plan that call for the use of quarantine and other imposed types of enforcement should influenza or any other infectious disease cause a pandemic.

"Never use the police or the military," Henderson told a meeting organized by the University of Pittsburgh Medical Center's Center for Biosecurity, where he works. "Once we brought military or police in, we found many citizens retired to the woods," he said Tuesday.

When health teams tried to quarantine families, had a similar response. "People hid," he said. "They didn't want to be quarantined so they hid cases."

As H5N1 avian influenza spreads in birds across Asia, Europe and into Africa, global health officials are trying to switch into high gear to control it. But they are running into problems with local residents in many places, including most recently the village of Kubu Simbelang on the Indonesian island of Sumatra, where six people died from H5N1 infection.

"They are not angry, just unfriendly. They are unfriendly to the people from the central government, the provincial government," said Sidharta Pinem, head of animal husbandry in the region.

WINNING TRUST

Henderson said the drive to eradicate smallpox, which was eliminated in 1979, relied heavily on winning people's trust.

"What was the most effective was the support from religious leaders and village leaders," he said. For instance, they found they could train villagers to administer the vaccine, which is given using a fork-like needle that scratches the vaccine fluid into the skin.

"How responsive and enthusiastic and reliable these people were," Henderson said. "The only thing we could pay these people with was a thank you."

And an unexpected resource came from the youngest citizens. "For detection of cases we relied on schoolchildren," Henderson continued. "What is remarkable is how much 9- to 12-year-olds know about what is going on in their communities, and how willing they are to tell you."

Henderson said his team showed the children pictures of what a person looked like with the distinctive smallpox pustules and asked them if anyone in their communities seemed infected. Sometimes their information was more reliable than word from official sources, he said.

Henderson said he was concerned that the U.S. national pandemic plan includes the possibility of forced quarantine of travelers and perhaps of affected areas. Henderson does not believe quarantine works.

When severe acute respiratory syndrome (SARS) hit Canada in 2003, quarantine and isolation were used to try to control the respiratory infection. Some people who worked in hospitals developed fevers and respiratory symptoms.

"But they made the decision that they were so key to what was going on in the hospital that they came in to work," Henderson said.

Hospitals ended up being a source of SARS infection for many of the nearly 800 people who died from the virus before it was brought under control.

"So many people in so many professions feel they are key," Henderson added.

Any flu plan, Henderson feels, should do more to incorporate community organizations. He cited Rotary International, which has raised hundreds of millions of dollars for global polio vaccination campaigns, and Brazil, which eradicated polio by holding an annual Carnival-like mass vaccination festival.

May 22, 2006

CHONBURI, Thailand -- Inside a ramshackle Buddhist temple here on the country's southeastern coast, curious villagers gathered last fall as part of the United States' biggest gamble yet on stopping the AIDS pandemic.The informational meeting was almost like a game show as attractive young hosts revved up the crowd, working up to the big question, boomed out over loudspeakers: Would the audience be willing to volunteer to test an experimental HIV vaccine?

Cambodian Sex Workers Protest

Yunang Soma joined other Cambodian sex workers in November 2005 to protest a drug trial for tenofovir, a possible AIDS vaccine. "If the trial is so good, why don't they get sex workers from their own country? Why do they come to a poor country?" asked Soma. The protest led Cambodia's leaders to cancel the trial and oust researchers from the country.

The villagers hesitated. No one moved for a full 60 seconds. Then, tentatively, they approached the three stands set up at the front, marked "Join," "Not Join" and "Unsure."

For the past three years, such gatherings have been held all over Thailand, exhorting young adults to take part in the largest, most expensive, most resource-intensive AIDS vaccine trial ever. Funded by the National Institutes of Health, it ultimately will involve 16,000 people and last 3 1/2 years.

But as the trial moves forward, at a cost of more than $120 million, some researchers are raising questions about its validity. They disparage its science, question its ethics and doubt its efficacy.

One of the chief dissenters is Robert C. Gallo, who helped discover the human immunodeficiency virus. He scoffs at the notion that the trial will be successful. "I thought we'd learn more if we had extract of maple leaf in the vaccine," he said derisively.

NIH scientists defend the study, arguing that even if the vaccine doesn't work, the trial may reveal new things about HIV. "With 5 million new infections each year, the luxury of time is absent," four researchers wrote in the journal Science.

Vaccine Is Elusive

When scientists identified HIV as the cause of AIDS 21 years ago, they predicted that a vaccine to prevent the infection would be ready long before a treatment for the symptoms could be developed. The opposite turned out to be true. Many people today, especially in wealthy countries, are keeping the virus in check with drugs, but a vaccine, desperately needed in poor countries, has eluded modern medicine.

Despite years of effort, investment in the billions of dollars, and dozens of small tests in people around the world, there's still no scientific proof that a vaccine is even possible. HIV is a diabolical virus that disables the very immune responses a vaccine needs to trigger in order to work.

And yet the need is so urgent that scientists have gone forward with preliminary human tests of many vaccines on the basis of data they acknowledge is weak. The one in Thailand is the largest.

The fact that no one has ever been cured of AIDS increases the urgency of finding a vaccine. "In contrast to virtually every other microbe we've come across, there isn't a documented case of anyone who . . . ultimately cleared HIV from the body completely. That's why more and more research is being directed at trying to stop infection from happening in the first place," said Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases, part of the NIH.

The U.S. government last year spent 22 percent of its $3 billion AIDS research budget on vaccines and other preventive drugs, compared with less than 8 percent a decade ago. (Most of the rest is devoted to developing treatments or a cure for those already infected.) Meanwhile, the Bill & Melinda Gates Foundation this year designated up to $360 million for AIDS vaccine research, and Congress is encouraging more research with bills that would provide liability protection and tax benefits for drug companies.

But the science is daunting and subjects hard to come by. Scientists have been forced to travel to remote corners of the world to find communities where the infection rate is high enough to show results in a reasonable amount of time.

Thailand, where AIDS is a leading cause of death, has been among the most accommodating places. The NIH effort there involves two vaccines that individually have been disappointing in previous trials. One of them, developed by a once-revered scientist in the AIDS world, flopped spectacularly after an expensive test funded by private investors. The other showed little promise in early trials. Researchers cling to the hope that using them simultaneously will attack different aspects of the disease and prove effective.

Disappointing Trials

A vaccine is basically a trick: Take a germ or part of a germ, kill it or alter it so that it doesn't cause disease, then inject it into the body. The body thinks it is being attacked and produces an immune response that will protect it when it is exposed to the real thing.

But because HIV comes in 11 subtypes that constantly mutate, it must be treated differently. Enter Donald Francis, a longtime government researcher who is credited with helping to eradicate smallpox and develop vaccines for Ebola and hepatitis B. Francis had great credibility in the AIDS community. He was immortalized as an early hero in Randy Shilts's book "And the Band Played On" because he recognized the danger of AIDS long before it became an epidemic and argued forcefully for government action.

In 1982, he left public service to work for biotechnology giant Genentech Inc. and concentrate on AIDS full time.

His idea was to try to use the protein envelope that surrounds HIV to try to trick the body into thinking the whole virus had invaded it. When he injected it into a group of chimpanzees and then exposed them to HIV, they were protected. Francis then injected the cloudy liquid into his arm and became human research subject No. 1. There were no side effects, or none that he could notice. When he drew his blood he saw something promising -- a strong antibody response. Antibodies, proteins that form in response to invaders, typically protect a person against infection.

The big question was: Would that be enough to stop HIV infection?

Based on the preliminary trials, many scientists were skeptical. Nine of the 499 U.S. volunteers who had received Francis's vaccine subsequently became infected with HIV -- not from the vaccine but from later sexual exposure to the virus. While Francis was not concerned with those "breakthrough infections," other scientists were. "It is not the fact of breakthroughs that is so disturbing," John P. Moore of Cornell University's medical college said at an international AIDS conference in 1996. "It is the individual cases where there was a good vaccine response but infection occurred nonetheless." Researchers feared that the virus mutated so quickly that antibodies were ineffective against it.

Other scientists turned to a new technique, using snippets of the virus to promote a response from another part of the immune system, which activates "T-cells" instead of antibodies to attack germs. Most vaccine candidates in human trials today use that strategy.

Jay A. Levy, an AIDS researcher at the University of California at San Francisco, said he believes that the cellular approach is the only one that will work. "You aren't going to prevent HIV infection by the classic vaccine model," he said.

But Francis was not dissuaded. He took his data to the NIH and asked for funding to test his vaccine in a large group of humans. He ran into a wall of opposition.

Moore and Dennis R. Burton of the Scripps Research Institute argued in the journal Nature Medicine that funding for vaccine trials is limited, that patient cohorts are precious resources, and that "a social and political price" would be paid for a vaccine that failed in a large-scale trial.

The NIH turned Francis down. Ever persistent, he decided to rely on private funding. He persuaded Genentech to invest $2 million in a spinoff company, VaxGen Inc., and embarked on a cross-country tour that raised $150 million from other private investors.

With that money, the trial began in 1998, mostly in gay men in the United States, Canada, Puerto Rico and the Netherlands and in intravenous drug users in Thailand -- a total of 7,500.

Punnee Pitisuttithum of Mahidol University in Bangkok, who coordinated the Thai portion of the study, remembers being holed up in a San Francisco hotel room in 2003 studying reams of data. On the fourth day, the computers spat out the final analysis. The incidence rate for those who got the vaccine was 3 percent and the incidence for those who did not get the vaccine was 3 percent. There was no difference.

Punnee, 48, ran to her room and wept. "It took us nine years to find out the VaxGen vaccine did not work," she said.

Still, Francis latched on to an interesting blip in the analysis of African Americans. Fewer of the patients who got the vaccine were infected with HIV, but there were too few volunteers to draw any conclusions. For Francis it was a signal that perhaps the vaccine was indeed doing something to help prevent infection, if only in one segment of the population.

Critics brushed off that opinion, calling it a desperate attempt to salvage something from all the years of work. Weeks after the announcement that the vaccine had failed, VaxGen was hit with a shareholder lawsuit that accused the company's officials of continuing to make positive statements about their vaccine to artificially pump up the company's stock price, despite mounting evidence that it was not effective. The suit was dismissed last year and VaxGen, under new management, remade itself into a biodefense company.

"We were naively optimistic" back then, Francis said. "Our understanding of the technology to create an AIDS vaccine is still a black box and it's going to be a long haul."

In 2005, he quit his job as president of VaxGen and founded Global Solutions for Infectious Disease, a nonprofit organization that aims to develop an AIDS vaccine. Francis works in a basement office south of San Francisco that looks more like a file room than a laboratory. After VaxGen abandoned their project, he and his researchers struck out on their own. Four of the five researchers work without pay, draining their personal savings to pay for their research as they apply for grants. Francis said recently that he expects funding from a foundation in the coming month.

Hard Sell

Francis is no longer involved in testing the VaxGen vaccine. But the failure of the big 2004 trial did not stop its inclusion in the current trial, which was begun by the U.S. Army and subsequently taken over by the NIH. Half a world away in Thailand, that effort continues.

The Thai government has approached recruiting for the trial like the U.S. government did for the military during World War II -- with a call for patriotism and a plea for people to think of the greater good.

"You! Your family! Your community! Join your hands together to develop an HIV vaccine," said a yellow banner hoisted on storefronts and government buildings. Another sign, featuring a smiling woman, told young people to go to their nearest health center to get more information.

The recruiters in December exceeded their goal of enrolling 16,000 volunteers. Test subjects will receive either a placebo or a combination of two vaccines -- Francis's and one by Sanofi Pasteur SA of Lyon, France, that targets T-cells. The study will conclude in 2009, after all participants have been followed for 3 1/2 years.

The idea behind the NIH trial is that maybe vaccines need to provoke both antibody and T-cell responses to protect the body from AIDS. Critics say that the potentially confusing inclusion of Francis's vaccine muddies the issue and that it should be dropped from the study.

Nearly two dozen prominent AIDS researchers wrote an opinion piece in the journal Science in early 2004 calling Francis's vaccine "completely incapable of preventing or ameliorating" HIV infection and questioning "the wisdom of the U.S. government's sponsoring" the Thailand trial. "There are adverse consequences to conducting large-scale trials of inadequate [HIV] vaccines. . . . One price for repetitive failure could be crucial erosion of confidence by the public and politicians in our capability of developing an effective AIDS vaccine."

Last summer, Sen. Tom Coburn (R-Okla.), a physician, and other members of Congress began pressing U.S. officials to cut government funding to the trial, to no avail.

While the controversy over the trial continues in scientific and political circles in the United States, it has not been an issue in Thailand. At the Buddhist temple that evening in November, nearly all the 174 villagers eventually overcame their hesitation and said they would be open to serving as human test subjects.

Jo, a 19-year-old mechanics student with a goatee and buzz cut, signed up in the fall and brought eight friends to a clinic one morning so that they could get more information to decide whether they, too, wanted to be test subjects.

Jo said he doesn't care about the $7.50 he will be paid for each visit or any personal benefit he will get from the trial. It's important "to do something good for the community," he said.

That thought was echoed by Supachai Rerks-Ngarm, the principal investigator for the vaccine study and an official with the Thai Ministry of Public Health, who said that when it comes to researching an AIDS vaccine, there's no such thing as wasting time or money. "If we decide not to do it," he said, "we cannot explain that we have done our best to help our people."

May 21, 2006

Mosquitos being tested to be vaccinators against malaria

Associated Press

Two British scientists are using genetically engineered mosquitoes as flying syringes to try to vaccinate people against malaria and other diseases. Professor Bob Sinden of the University of London's Imperial College and Professor Julian Crampton of Liverpool University's School of Tropical Medicine say they have taken a key step in the process but still have a long way to go. The two scientists received a patent last year, but their technique is only being publicized now following areport by Derwent, a scientific information company.

"The key thing that we're doing is using the mosquito as the syringe," Sinden said in an interview Monday. "We are using malaria as an example." What the scientists are trying to do is similar to what was done in developing the polio vaccine: take bits of the parasite that causes malaria and put it into the body so the body builds up its own immunity. Malaria is transmitted to humans by the bite of an infectedmosquito. The scientists' idea is to use genetically engineered mosquitos that vaccinate the people they bite instead of giving them malaria. "In the world you have 400 million cases of malaria a year, and what we are looking to do is produce vaccines against this disease," Sinden said. "What numerous scientists are doing are looking for parasite proteins that are critically important for growth of the malaria, and then to immunize people with those proteins, and this will then incapacitate the malaria parasite," he said.

In their technique, a genetically engineered mosquito would transfer a protein through its saliva which would act as a vaccine to immunize a person against malaria. The trick is to modify the insect's salivary gland by introducing a parasite gene that produces an antigen known to stimulate the body to resist the malaria parasite, Sinden said. "We have successfully taken a malaria gene and put it into a mosquito salivary gland where the parasite protein is made and then used the salivary gland to immunize a mouse so that the mouse will not transmit malaria,"he said. Crampton's team of researchers introduced the gene into isolated salivary glands from the mosquito, he said. What the scientists now have to do - "and this is a huge step" - is to carry out the experiment in a live mosquito instead of in a test tube so when it bites "it spits the parasite protein which will immunize you against malaria," Sinden said. "The big problem that we've got is that the technology for introducing genes into whole mosquitos is only just emerging, and until that step is completed, we are still talking of a theory," he said.

But the scientists are optimistic the technique will emerge in the near future. Potentially, the technique could be used to immunize people and animals against a wide range of diseases, and any biting insect could be used to carry the vaccine, not just mosquitoes, Sinden said. "We are extremely cautious about testing these mosquitoes in closed laboratory colonies, and we have no intention of releasing any genetically engineered insect without full and detailed technical and safety considerations," he said.

May 17, 2006

Fishing: The Best Medicine

Vance Wasden, a local veteran with disabilities, holds a fish caught on the Smith River in Montana. A free float trip was provided to disabled veterans recently.

For Vance Wasden, a local disabled veteran, wet flies and tapered leaders have been the best therapy for coping with health problems incurred in the line of duty.

And he's found no more therapeutic waters than the Smith River in Montana - one of the few rivers anglers must vie for hard-to-get permits to fish.

He returned from a float trip offered free to disabled veterans last Friday.

The food was gourmet, but the fishing was better.

Mike Geary, of Lewis and Clark Expeditions in Helena, Mont., and his clients provided the trip of a lifetime for the veterans.

“You go into the military. Everyone's healthy and young. Then you get messed up in the Gulf,” Geary said. “You go through as many mental issues as physical issues.”

Wasden, who is considered 100 percent disabled by the military due to complications from a bad anthrax vaccine he was forced by the U.S. military to take, is so convinced that fishing is the best medicine he's now working to establish local fishing programs for other area disabled veterans.

Wasden would like to create a local chapter of Project Healing Waters, which solicits donations to take disabled veterans on free fishing trips.

He also hopes to form a team of disabled veterans to compete in a world fishing competition for people with disabilities. He will likely recruit many of the friends he made on the Smith River - including a sniper who'd lost a leg and a kid from Salt Lake city whose legs were mangled from a roadside bomb.

Using a fly rod and mostly wet flies, Wasden landed several 18-inch rainbows and browns, and one 29-inch rainbow.

They saw deer, elk, antelope, nesting bald eagles and even a mountain lion atop a sheer cliff wall above them as they floated.

They stopped to explore a cave along the banks and found several American Indian petroglyphs.

“It really was the trip of a lifetime - not just the food, scenery and fishing, but also the camaraderie aspect of it,” Wasden said.

They released all of the fish they caught but ate well nonetheless. Each time they banked, they were served hors d'oeuvres. For dinner they dined on rosemary chicken, plank salmon, steak and cheesecake.

Wasden's disability surfaced between the first war and the current conflict in the Persian Gulf, where he was stationed. He has problems with fatigue, bad headaches, internal bleeding, seizures and other health concerns. He also has trouble walking.

He's had to learn to adapt. Wasden, a left-handed man, now casts his fly rod with his right hand because the movement in his left arm is restricted.

His medical condition was profiled last summer by an east coast film crew doing a documentary.

Wasden and his wife, Michelle, share their Pocatello home with five children, a dog, cats and a goat named Goat.

“Most all of the services for disabled veterans are back east and down south,” Wasden said. “Pocatello has a lot of disabled veterans in of itself.”

Project Healing Waters

For more information on Project Healing waters, e-mail Vance Wadsen at vmwasden7@aol.com.

May 15, 2006

Officials mull using poultry vaccine on people

Canadian Press

TORONTO -- Is what's good for the goose good for Mr. and Mrs. Gander? Public health authorities exploring the possibility of protecting people against an influenza pandemic with vaccine produced for poultry say "Maybe."

The World Health Organization and others are studying whether it would be possible to tap into the global agricultural vaccine production capacity to help bridge the enormous gap between the amount of human flu vaccine the world can produce and how much would be needed in a severe pandemic.

While the idea of giving people vaccine produced for poultry may seem, well, for the birds, the proposal - advanced by eager agricultural vaccine-makers - hasn't been dismissed out of hand.

"I think it's something that does merit consideration," says Dr. Jesse Goodman, director of the U.S. Food and Drug Administration's Center for Biologics Evaluation and Review. (Vaccines are considered biological products.)

Goodman and others would rather not have to resort to this option, hoping a pandemic is far enough off and new investment in novel production methods and facilities is sufficient to vastly expand output within the human influenza vaccine sector.

But given the current limited vaccine capacity, all sorts of options would have to be on the table if a harsh pandemic were to strike soon. And harnessing agriculture vaccine production is one of them, Goodman says.

"I would say our goal would be to keep an open mind about possible approaches in an emergency," he said in an interview from Washington.

"For a medium-to long-term approach, certainly enhancing the capacity and use of the human vaccines in my mind would be the first priority. . . . (But) in the short-term emergency point of view . . . I think it is wise to look at all possible approaches and alternatives."

Canada is unlikely to need to explore this option. The country has a long-term contract for pandemic vaccine to be made at a production facility located in Ste-Foy, Que.

But most other countries, including the United States, currently don't have enough domestic production capacity to be able to vaccinate their citizens during a flu pandemic - hence the outside-the-box exploration of options.

Experts say the agricultural vaccine sector's greatest potential for humans lies as a possible source of antigen (vaccine-ready virus) for live attenuated vaccines such as FluMist, the inhaled vaccine produced by MedImmune Inc., headquartered in Gaithersburg, Md.

That's because antigen used in live attenuated vaccines is not put through the investment-intensive purification and sterilization processes used in the manufacture of inactivated (killed virus) vaccine, the type contained in flu shots.

The production processes for live attenuated vaccine and agricultural vaccine are quite similar, says Dr. Klaus Stohr, the WHO's special adviser on influenza pandemic vaccine development. So are the criteria - known as good manufacturing practices - set down for production of agricultural and human flu vaccines.

"So theoretically - theoretically - it's conceivable that this antigen, and there's a lot of antigen produced by the agricultural vaccine makers, could with much less investment be transformed into live attenuated vaccines," Stohr says.

A MedImmune executive says the company doesn't yet know what to make of the idea, raised at a recent meeting in Geneva hosted by the WHO.

"We're just beginning to discuss this in MedImmune and we really haven't looked into it to be able to understand what that would mean," says Kathleen Coelingh, senior director of scientific affairs.

"We're not ruling anything in or anything out."

Goodman says companies which make inactivated flu vaccine might also be able increase their output by processing some antigen produced by agricultural vaccine makers.

But Stohr says human flu vaccine makers carefully match their antigen production to their capacity to purify, sterilize, bottle and label, suggesting these essential downstream steps create a bottleneck around which there is no easy or inexpensive route.

Dr. David Fedson, a retired vaccine industry executive, says there are hitches that may limit the ability to use antigen from agricultural sources to vastly increase the output of live attenuated vaccine as well.

FluMist, for instance, currently must be kept in a freezer until it is administered - a factor that might limit its usefulness in some parts of the world. As well, individual doses come pre-packaged in an inhaler, raising questions about whether adequate numbers of additional inhalers could be made and whether MedImmune or another company could expand capacity to package mass numbers of extra doses.

Modifying the delivery mechanism so that the vaccine is given in the form of nose drops could get around that potential bottleneck, Fedson says. (The Russians have been using live attenuated vaccine delivered this way for at least two decades.) But changing the vaccine would require regulatory approval.

Still, Stohr insists that with few options for rapidly and affordably increasing human flu vaccine production capacity, the notion of exploiting agricultural antigen sources is worth further study.

"There are so many things which we have seen may not work out quickly or will cost too much," he says.

"But here we have an option which has not been fully explored which has a good chance or which has a greater chance of success. And if it succeeds, it would make a profound contribution to the efforts to fill the pandemic vaccine gap."

Bush Uses FDA To Shield Big Pharma From Lawsuits

By Evelyn Pringle

In January 2006, the FDA announced the Bush administration's latest gift to Big Pharma in a statement that said people who believe they have been injured by drugs approved by the FDA should not be allowed to sue drug companies in state courts.

"We think that if your company complies with the FDA processes, if you bring forward the benefits and risks of your drug, and let your information be judged through a process with highly trained scientists, you should not be second-guessed by state courts that don't have the same scientific knowledge," said Scott Gottlieb, the FDA's deputy commissioner for medical and scientific affairs.

To soften the blow, the agency's claim of federal preemption was included as a preamble to the long sought after new drug labeling guidelines. In response to the FDA's statement, Senator Edward Kennedy (D-MA) issued a statement of his own that said: "It's a typical abuse by the Bush Administration -- take a regulation to improve the information that doctors and patients receive about prescription drugs and turn it into a protection against liability for the drug industry."

The ploy was also readily recognized by state lawmakers and trial lawyers as another ploy to reduce the public's ability to hold Big Pharma accountable. "Eliminating the rights of individuals to hold negligent drug companies accountable puts patients in even more danger than they already are in from drug company executives that put profits before safety," said Ken Suggs, president of the Association of Trial Lawyers of America.

"The fact that the drug industry can get the FDA to rewrite the rules so that CEOs can escape accountability for putting dangerous and deadly drugs on the market is the scariest example yet of how much control these big corporations have over our political process," Mr Suggs told the Washington Post.

According to Attorney Mark Labaton, a partner at the firm Kreindler & Kreindler, LLP, with offices in New York and LA, "the Administration's recent efforts to misuse federal rulemaking in the pharmaceutical and other areas to eviserate consumer rights is a big step backward."

"The new FDA rules to limit consumers' rights," he says, "are part and parcel of a larger effort to deny persons injured by unsafe products -- be they drugs, cigarettes or automobiles -- any form of redress."

"Clearly," Mr Labaton notes, "this Administration and its supporters want to slam the courthouse doors on working men and women injured by unsafe products.

He says its ironic that "an Administrative that calls itself "compassionate" and "conservative" consistently turns its back on "limited government" and "states rights" when it comes to protecting the rights of seriously injured consumers."

Upon learning of the FDA's power grab, the National Conference of State Legislatures, a bipartisan group that represents state lawmakers, accused the FDA of trying to seize authority that it did not have. The organization bases its opposition, in part on the following:

"FDA has usurped the authority of Congress, state legislatures and state courts. There is no statutory authority in the FDCA for FDA to preempt state product liability laws as they relate to prescription drugs.

"Instead of seeking valid congressional authority, unelected agency officials are seeking to preempt state product liability laws by writing this preemption into a final rule, thereby undermining state policy and judicial decision made in this area.

"State tort laws and civil justice systems serve as an important check on federal standards. Our civil justice system establishes a duty of care that protects citizens when the federal government is too slow to act or when federal standards are insufficient. States have the ability to achieve greater protections for their citizens through successful product liability lawsuits."

In an earlier gift delivered to Big Pharma in December 2005, Republican leaders, and specifically Senator Bill Frist (R-TN), attached protective provisions to a Department of Defense appropriations report that gave the industry “unprecedented immunity," according to Democratic lawmakers who described the underhanded move as follows:

"Republican leaders added provisions to the conference report after cutting a back-room deal in the middle of the night. The conference report grants sweeping immunity to drug companies for injuries caused by vaccines and drugs and for the administration of those vaccines and drugs, even if they are made with flagrant disregard for basic safety precautions.

"Moreover, the compensation program is a sham, leaving people who become injured from a drug or vaccine without recourse.”

Since 2002, Senator Frist had tried numerous times to insert this rider in Homeland Security Bills after thousands of lawsuits were filed by parents who believe the mercury-based preservative thimerosal, contained in childhood vaccines until recently, caused autism and other neurological disorders in their kids.

The rider could save Big Pharma hundreds of millions, if not billions of dollars.

The latest revelation on this little stunt came on May 8, 2006 when the Tennessean reported that vaccine industry officials helped shape legislation behind the scenes that Frist secretly amended into a bill, according to e-mails obtained by Pubic Citizen, a public advocacy group.

The industry group, called the Biotechnology Industry Organization, wanted the vaccine liability language in the bill, the e-mails proves.

"At Senator Frist's staff's request, this morning, BIO (Tom and I) participated in a meeting with three other industry representatives (Sanofi and an outside counsel who works for both Pfizer and Roche, I believe), administration staff (HHS, DoJ and WH Leg Affairs), and Liz Hall to further discuss liability," BIO official Dave Boyer wrote in a November e-mail obtained by Public Citizen.

Other E-mails and documents show that BIO met privately with Frist's staff and the White House to figure out ways to give drug makers protection from people injured by vaccines.

"The lack of any restriction on jury trial is problematic," the BIO analysis said. "Where injured parties have no other avenue for relief, juries are likely to find ways to award damages."

In another e-mail, Boyer described a meeting in which Karl Rove said it was "important to the President that a bill move this year," and said "they hadinvited industry to discuss what they understood to be a few key remaining points" of contention.

Republicans members of Congress had tried to on several occasions to enact similar legislation of its own, but with voters already so angry over soaring drug costs, they finally had to back off.

With less than 3 years left in office, and the Democrats positioned to take over Congress in the fall elections, Bush had to find a way to repay Big Pharma so he came up with the bright idea to utilize the FDA and kill 2 birds with one stone.

This route would spare Republicans the task of trying to pass pro-industry legislation in an election year and still reward Big Pharma for the more than $80 million that Republicans received from drug makers over the past decade.

Since 2000, the top drug corporations, their trade group, and their employees gave more than $10 million to 527 organizations, tax-exempt political committees which operate in the grey area between federal and state campaign finance laws, according to Drug Lobby Second to None, July 7, 2005, M. Asif Ismail.

Nearly $87 million of the contributions went to federal politicians, with almost 69% going to Republicans. Top recipients include Bush, with upwards of $1.5 million, and members who sit on committees that have jurisdiction over pharmaceutical issues, reports Drug Lobby Second to None.

During Bush's campaigns, 21 pharmaceutical industry executives and lobbyists achieved "Ranger" or "Pioneer" status, which means they raised at least $200,000 or $100,000, respectively, during the 2000 or 2004 campaigns.

According to Public Citizen, the group included 5 executives from brand-name drug companies, 6 officials from HMOs, the CEO of a pharmacy services company that runs a PBM, the head of a direct-mail pharmacy, and 8 Washington lobbyists who represent drug companies and HMOs.

Frist is never shy when it comes to calling in markers from drug companies. In November 2004, when he wanted to take a victory tour celebrating the newly elected Republican senators, "A Gulfstream corporate jet owned by drug maker Schering-Plough was ready to zip the Senate majority leader to stops in Florida, Georgia and the Carolinas," according to the April 25, 2005 USA Today

Frist's PAC reimbursed Schering $10,809, the equivalent of a commercial first-class fare, but that was only a fraction of the cost of a charter flight, which would have cost 3 times that much. Besides, the cost was almost a wash because Schering had donated $10,000 to Frist's committee in 2003-04, according to USA Today.

Its also worth pointing out that Big Pharma was the largest contributor to the National Republican Senatorial Campaign Committee while Frist chaired the Committee.

The ever-growing number of lawsuits in state courts has created a nagging fear in drug makers. Local juries and elected judges in state courts are much more likely to go against drug giants than juries and appointed judges in federal courts which is a one of the main reasons why Big Pharma wants all cases moved to federal courts.

Vioxx set off the industry's worst nightmare when users or their heirs began filing lawsuits all over the US. According to the January 24, 2006, Associated Press, Merck currently faces 9,200 Vioxx lawsuits, with about 4,050 in federal courts and the rest in state courts.

But Vioxx by far is not the only worry for Big Pharma. These days, every major drug company has litigation problems involving one or more FDA-approved products and a few prominent law firms have taken up the battle for plaintiff's in state courts.

For instance, since 1990, the Los Angeles based Baum Hedlund Law Firm has been handling SSRI (selective serotonin reuptake inhibitor) suicide/violence cases and served on the Plaintiffs' Steering Committee in the first SSRI-suicide litigation involving Prozac, the first SSRI approved by the FDA.

Baum Hedlund partner, Karen Barth Menziess, has been litigating claims involving injuries stemming from SSRIs such as Prozac, Paxil, Zoloft and, more recently, Lexapro/Celexa, for over a decade.

She heads a team of attorneys, who have successfully defeated Pfizer's and the FDA's preemption arguments in a number of cases, including Motus v Pfizer and Witczak v Pfizer.

In addition to her court activities, Ms Menziess has testified about the dangers of SSRIs before the California State Assembly and the FDA's Psychopharmacologic Drugs Advisory Committees and met with members of Congress regarding the risk of antidepressant induced suicidality and preemption issues.

Ms Menziess wrote an article discussing the ill-effects of preemption in Mealey's Emerg. Drugs & Devices 27 (2006), titled, "Preamble To FDA Final Rule: FDA's Latest Effort To Immunize Drug Manufacturers From Tort Liability At The Expense of Consumer Safety," and stated in part:

"Pharmaceutical industry lobbying efforts and zealot tort reformers have sired a new wave of brazen attempts to shield drug manufacturers from tort liability.

"The preemption language in the preamble to the Final Rule is but the latest attempt. Preemption has become the argument du jour and politically appointed regulatory officials the mouthpieces. The crafty messages sound of consumer protection, but are just the opposite. Limiting the liability of drug companies will not improve public safety.

"The FDA s purported position on preemption assumes that the FDA is infallible and that negligent misconduct by pharmaceutical companies should be the sole purview of FDA. Recent regulatory failures demonstrate that FDA is neither infallible nor does it have the capability of policing drug manufacturers negligent misconduct."

The Bush administration went up against a tough opponent in Baum Hedlund when it turned to the courts, and had the FDA file amicus briefs hoping the courts would rule in favor of preemption, but those attempts also failed.

Ms Menziess explains some of the history of the FDA's intervention into lawsuits she was involved in stating: "Until his resignation in late 2004, FDA Chief Counsel, Daniel Troy, was the pharmaceutical industry's 'inside man,' filing legal briefs on behalf of former clients such as Pfizer (the maker of Zoloft) and soliciting defense attorneys to submit their cases for government amicus brief consideration."

"Although the newly appointed Chief Counsel, Sheldon Bradshaw, lacks the blatant pharmaceutical industry ties that Troy had," she advises, "he clearly was not selected to his position because of a sudden change-of-heart in the political leadership or direction of the FDA."

The FDA filed its first brief in favor of a manufacturer of SSRIs in September 2002 in Motus v Pfizer, one of Baum Hedlund's cases in California, which was pending in the 9th Circuit Court of Appeals.

Daniel Troy, who was the FDA's Chief Counsel at the time, was contacted by Pfizer's national counsel, Malcolm Wheeler, in the summer of 2002 requesting that the government get involved in this private lawsuit to help Pfizer with its preemption argument related to Zoloft-induced suicidality.

Despite the fact that Pfizer had been one of his clients and Troy was paid over $358,000 for work he had conducted for Pfizer in the year he took office, Troy acquiesced, arguing that there was no impropriety in doing so because he did not become involved until after the required 1-year period in which government employees may not participate in official activities involving former clients.

From public accounts, it appears that the 1-year "grace period" elapsed less then a month before Troy entered the fray.

Troy argued in the FDA brief that, even though Pfizer never sought to strengthen Zoloft's warning label concerning suicidality, any warning, no matter how worded, that suggested a link between Zoloft and suicidality would have been false and misleading, would have misbranded the drug, and the FDA would have rejected any effort by Pfizer to use such a warning.

The 9th Circuit never decided the preemption issue, instead ruling on another appellate issue, which concluded the case on unrelated grounds.

Nevertheless, Menziess said that Pfizer has continued to use the brief in its battle against Zoloft-induced suicide cases, arguing that the lawsuits are federally preempted and should be dismissed.

But Judges across the US have been rejecting Pfizer's arguments, as well as the FDA brief itself. A federal judge in Texas pointed out that the law "allows, even encourages, manufacturers to be proactive when learning of new safety information related to their drug."

"Manufacturers, not the FDA, are tasked with the responsibility of taking proactive steps once a manufacturer learns of 'reasonable evidence of an association of a serious hazard with a drug,'" the judge stated.

A state court judge in California ordered the FDA brief stricken from the record, calling it "hearsay and irrelevant."

In an Illinois case, the judge said the brief "contains nothing more than legal argument by [FDA] counsel."

In a Zoloft suicide case in Minnesota, the court rejected Pfizer's arguments, stating that it "declines to treat statements from a single FDA legal brief as declarations afforded the preemptive force of law." The same judge also called Pfizer's arguments "perverse" and a "public policy argument gone awry."

Ms Menziess notes that the FDA's legal stance on preemption is "particularly egregious in the wake of congressional investigations involving FDA failures to protect the public health, in particular related to antidepressants."

Without state liability laws, she says, drug companies will be able to escape liability for injuries and deaths caused by drugs like SSRIs and Vioxx.

Baum Hedlund currently represents approximately 50 victims and their families in cases involving alleged antidepressant-induced suicide and suicide attempts, over one third of whom are children and adolescents.

As with Vioxx, the risks associated with SSRIs were also kept hidden. Ms. Menzies's litigation has evidence from as far back as the 1980's that people taking SSRIs were at a heightened risk of suicidality, and not just children, she notes.

In fact, in the early 1990s, it was the FDA safety officer Dr David Graham, of recent Vioxx fame, who raised concerns about the risk between antidepressants and suicidality, but no one listened, Ms Menzies says.

Fourteen years later, the FDA finally ordered black box warnings labels on SSRIs alerting physicians about the increased risk of suicidality. Ms Menziess describes the FDA during these years as "complacent, ignoring its own internal scientist when they raise concerns, and in the pocket of industry."

She believes that the FDA would never have confronted the issue had it not been for the public outcry from victims, consumer groups, courageous experts willing to place their careers on the line, investigative reporters and pressure from certain members of Congress; and yes, she says, "lawyers uncovering the drug industry's dirty little secrets through legal discovery and speaking out about the dangers."

Ms Menziess points out that "the antidepressant controversy and resultant congressional investigations, and later, the Vioxx public health debacle, have served to highlight deep-seeded problems within the FDA."

Over the past couple of years, a growing number of lawmakers have been turning up the heat on both the FDA and the industry in response to their combined failure to reveal the problems found in studies conducted on drugs like SSRIs and Vioxx.

At one point, Senator Charles Grassley (R-Iowa), Chairman of the Senate Finance Committee, came right out and accused the FDA of suppressing studies in order to protect industry profits and the careers of certain FDA officials.

"The Vioxx example showed that the FDA and Merck were too close for comfort," Senator Grassely told Health News on March 12, 2005. "Testimony and documents at our Finance Committee hearing showed that the FDA allowed itself to be manipulated by Merck," he said.

The results of a trial that took place in 2000, surfaced that showed that the FDA and Merck were aware that heart attacks were 5 times more likely in patients taking Vioxx than among those taking a similar drug, Senator Grassley pointed out, but the FDA did nothing to change the labeling for nearly 2 years, he said, while Merck marketed its product on nightly TV.

On November 18, 2004, Senator Grassley drew enormous media attention when he held hearings on Vioxx, and FDA scientist, Dr Graham, testified that he determined that Vioxx may have caused tens of thousands of heart attacks and strokes but that his superiors at the FDA pressured him to keep quiet.

To put the number of injuries into perspective, Dr Graham told members of the committee that instead of side-effects from a drug, to think of it as if they were talking about jetliners.

"If there were an average of 150 to 200 people on an aircraft," he said, "this range of 88,000 to 138,000 would be the rough equivalent of 500 to 900 aircraft dropping from the sky."

"This translates to 2-4 aircraft every week," he advised, "week in and week out, for the past 5 years."

"If you were confronted by this situation," Dr Graham asked the panel, "what would be your reaction, what would you want to know and what would you do about it?"

He noted the problems with the FDA's reliance on a 95% paradigm. In other words, he said, a drug is considered safe "until you can show with 95% or greater certainty that it is not safe."

The scientist condemned the FDA's failure to acknowledge the Vioxx risks sooner. "I strongly believe that this should have been, and largely could have been, avoided," Dr Graham told the committee.

Ms Menziess often cites his testimony to demonstrate that the FDA's position on preemption is wrong and states: "Dr. Graham's testimony illustrates why FDA approval and subsequent post-marketing acquiescence should have no preemptive effect."

The Vioxx matter caught the attention of the Senate Finance Committee basically because of the drug's cost to government programs like Medicaid and Medicare. The committee is responsible for oversight of the two programs.

At the November 18, 2004 hearing, Senator Max Baucus discussed the high-costs related to the drug: "In the 5 years that Vioxx was on the market, Medicaid spent more than $1 billion on the drug," he said.

In addition to the prescription costs, government programs are now paying for the damage caused by Vioxx. "Medicaid bears the cost of any additional medical care necessary when drugs cause injury," Senator Baucus pointed out.

By far, the Vioxx debacle is the most serious public health failure to occur since the FDA took on the authority for safety oversight of medical products in 1938.

On September 3, 2005, Shane Ellison, a former pharmaceutical chemist turned whistleblower and author of the book, “Health Myths Exposed,” gave an interview to Crusador Magazine and discussed Vioxx and the problems within the FDA.

According to Mr Ellison, the FDA and Merck knew about the dangers of Vioxx for at least 4 years before it was pulled off the market. "Instead of removing the drug immediately," he said, "they kept it on the drug market for matters of wealth not health."

Mr Ellison says compliant politicians have "democratized" the industry. "This means that drug approval is a matter of 51% telling the other 49% that deadly drugs are safe and necessary," he reports. "Science and choice no longer prevail at the FDA or at pharmaceutical companies," he added.

"To go against the 51% means losing your career," Mr Ellison explains. "Therefore, the majority of scientists choose to please drug companies, not the general public."

To substantiate this allegation, Dr Ellison points to Dr Curt Furberg, a member of the FDA's drug safety advisory committee. Dr Furberg went public with findings that Bextra also caused heart attacks and strokes and said studies “showed that Bextra is no different than Vioxx, and Pfizer is trying to suppress that information,” in the British Medical Journal.

"Immediately thereafter," Mr Ellison said, "Dr. Furberg was barred from serving on the panel that was responsible for considering the safety of cyclo-oxygenase-2 (COX 2) inhibitors."

"The end result being more votes in favor of COX 2 inhibitors, the drug company wins by votes – not science," he told Crusador. Another relevant, but little-mentioned fact, is that many FDA officials end up working for Big Pharma. "The old joke is that the FDA is sort of like a showcase for a future job in the drug industry," Robert Whitaker, author of Mad In America, said in an August 2005 interview with Street Spirit.

"You go there, you work awhile, then you go off into the drug industry," he said, "the progression that people make, in essence they're making good oldboy network connections, so they're not going to be so harsh on the drugcompanies."

In addition, when leaving office many federal employees and members of Congress go to work for Big Pharma in one area or another. For instance, of the 1,274 people registered to lobby in Washington for drug companies in 2003, according to an April 2005 report by the Center for Public Integrity, 476 are former federal officials, including 40 former members of Congress.

Critic say the Prescription Drug User Fee Act, is in large part to blame, for the current problems within the FDA. The Act allows the agency to collect a fee from a drug company seeking approval for a new drug. In return, the FDA is expected complete the review process within 12 months.

User fees now account for about 40% of the approval process, which means the FDA is dependent on drug companies for nearly half of its funding. This situation creates a major conflict of interest according to Dr Graham: "This culture views the pharmaceutical industry it is supposed to regulate as its client. It overvalues the benefits of the drugs it approves, and seriously undervalues, disregards and disrespects drug safety," he told members of Congress.

Another problem he said is that even when the FDA does try to take measures to limit harm, the agency lacks the authority to force drug companies to comply. For example with Vioxx, he said, it took more than 2 years to get Merck to add the increased risk of heart attack and stroke on the label.

Then there is the matter of the conflicts of interests involving the FDA panels that advise the agency on which drugs should be approved, what their warning labels should say, and how studies should be conducted.

The approximately 300 experts on the 18 committees make decisions that affect billions of dollars in sales and with very few exceptions the FDA follows their advice.

Members of the panels are supposed to be free of conflicts of interest relating to products they consider but they rarely are. For example, in February 2005, when the hearings were held to determine whether the COX-2 inhibitors should be allowed to remain on the market, a panel mired with conflicts was exposed. Out of the 32 voting members, ten had served as consultants to Merck and Pfizer in recent years.

This revelation prompted Senator Mike Enzi, (R-WY), the chairman of the Health, Education, Labor and Pensions Committee, along with Senators, Edward Kennedy (D-MA), and Richard Durbin (D-IL), to ask the General Accounting Office to look into the FDA's practice of letting scientists serve on panels when they have conflicts of interest.

"We are concerned about the process that supports FDA's decisions to waive conflicts of interest rules for scientists with financial ties to the manufacturers of the products under consideration, or their competitors," said their letter to the GAO in September 2005.

"These practices appear to have undermined the public's faith in the objectivity and fairness of FDA's advisory committees," they wrote. The Senators specifically referred to the conflicts among the panels that studied the Cox-2 inhibitors like Vioxx.

According to Ms Menziess, "The FDA's preemption argument, if successful, would take away the sole means by which American consumers may obtain compensation for drug-induced injuries caused by a drug company's failure to warn."

"Civil lawsuits uncover internal company documents to which not even the FDA has access," she explains.

"The tort system provides an important check on the regulatory process and on drug companies' compliance with law."

"Preemption," Ms Menzies warns, "would close off one of the few avenues by which we learn of safety and efficacy information that pharmaceutical companies do not publish or hide from FDA."

May 13, 2006

Racing to find a vaccine

By Alison Walker, News-Post Staff

FREDERICK -- Despite existing antibiotics and vaccines to treat and prevent anthrax, scientists aren't resting on their laurels four years after mail attacks in 2001 that killed five people. "We have to be looking ahead, thinking about what problems there might be in the future," said Arthur Friedlander, a senior scientist and anthrax expert at the U.S. Army Medical Research Institute of Infectious Diseases, the Army's biodefense laboratory at Fort Detrick.

"We think we have approaches to dealing with this organism now, but we can't be complacent about it," Mr. Friedlander said. "This (anthrax) was the one organism that was used."

Though an effective anthrax vaccine is available and a new one is in clinical testing, USAMRIID is one of several laboratories around the country studying additional ways to protect the body against anthrax.

New treatments would be critical in fighting infections caused by genetically engineered anthrax bacteria, Mr. Friedlander said. Anthrax strains with manufactured resistance to current vaccines and antibiotics remain a threat.

Next-generation anthrax

Several biopharmaceutical companies are developing next-generation vaccines against anthrax, an improvement on the licensed vaccine, anthrax vaccine adsorbed.

The next-generation vaccine, developed by Mr. Friedlander and a USAMRIID team, uses protective antigen, a protein secreted by the anthrax bacterium.

The protein, dubbed rPA, induces the body's immune system to produce antibodies against the bacteria's toxin and has been shown in USAMRIID studies to give a high level of protection against inhalation anthrax in nonhuman primates.

The National Institute of Allergy and Infectious Diseases, under the National Institutes of Health, is conducting clinical trials on the rPA vaccine.

The U.S. Department of Health and Human Services awarded VaxGen an $877.5 million contract in November 2004 to fund 75 million doses of rPA anthrax vaccine for the national stockpile, which could immunize 25 million people after a large-scale anthrax attack.

Protective antigen is the most protective protein ever discovered and the rPA vaccine is extremely effective, Mr. Friedlander said.

Mr. Friedlander's team announced May 1 a combination of anthrax adsorbed vaccine and antibiotics significantly improves survival after exposure. The study also suggested the combination treatment may allow for a shorter course of antibiotics. Antibiotics are typically prescribed for 60 days after exposures.

In their study, all monkeys exposed to airborne anthrax spores and treated several hours later with the vaccine and antibiotics survived and never developed infection. Only 44 percent of monkeys given just antibiotics survived.

Mr. Friedlander said he expects a similar study combining antibiotics and rPA vaccine, rather than anthrax adsorbed, would show equally good protection post-exposure against inhalation anthrax.

Boosting protection

Despite the vaccine's proven effectiveness in animal models, USAMRIID is studying additional components that could boost rPA's protection against anthrax.

"(rPA is) a spectacular vaccine," he said. "It's not as if it's not a superior vaccine -- that's why it was selected for advanced development."

One area of study by USAMRIID and other laboratories is a vaccine using both rPA and a capsule that surrounds the anthrax bacterium. The capsule makes the bacterium slippery, preventing the body's white blood cells from destroying it.

A vaccine based on this capsule allows the body to make antibodies that bind to the capsule, enabling white blood cells to destroy the bacteria.

USAMRIID proved the capsule vaccine provided protection against anthrax in mice in a late 2004 study. Mr. Friedlander said researchers are planning additional animal studies, including tests in nonhuman primates.

A combination of both rPA vaccine and capsule vaccine could provide considerable protection, he said, as each targets a different mechanism the bacteria uses to infect a host.

Targeting anthrax genes

USAMRIID researchers are also knocking out genes in the bacterium to determine the role each plays.

New therapies will target these abilities. Penicillin, for example, interferes with the bacteria's ability to make cell walls and divide.

Developing improved antibiotics involves studying what the anthrax bacteria need to survive in a host and to subvert the body's immune response, Mr. Friedlander said.

"If you damage one pathway, it doesn't necessarily mean the organism's going to stop growing," he said. "There's a lot of redundancy built in -- they're not stupid. Finding a critical, vital target remains a challenge."

Research will need to stay one step ahead of the anthrax bacteria to ward off the threat of antibiotic-resistant organisms, Mr. Friedlander said.

May 11, 2006

Shares of VaxGen Inc. plunged 37 percent yesterday after the company complained about new government requirements in its contract to produce an anthrax vaccine, characterizing them as so onerous and time-consuming the company isn't sure it will have enough money to complete the work.

VaxGen, of Brisbane, Calif., said it would file a legal claim in an effort to win more money from the government, on top of the nearly $1 billion it is already due to receive under several federal contracts. "I can say that we have an experienced legal team in place, and we believe we have a very strong case," said James P. Panek, senior vice president of manufacturing at VaxGen.

Investors were less sanguine, fleeing the shares after they realized that VaxGen, which once planned to start shipping its vaccine to the government and receiving payments early this year, probably won't be able to do so until 2008 or 2009. The delay means the company must raise tens of millions of dollars to keep operating while it tries to produce a vaccine acceptable to the government.

Administrators at the Department of Health and Human Services disputed VaxGen's characterization, saying the main action they took recently was to extend deadlines in the company's contract. Last night, HHS issued a statement at sharp variance with the company's interpretation of events, saying it had imposed no burdensome new requirements. Marc Wolfson, a spokesman for the agency, declined to elaborate or to say whether HHS had issued guidelines to the company fleshing out previous requirements of the anthrax contract.

Failure of the program, in which VaxGen is supposed to make enough anthrax vaccine to protect 25 million people from a terrorist attack, would be a big setback for the Bush administration's effort to develop national defenses against bioterrorism. Congress, responding to a call from the president in his 2003 State of the Union speech, passed the plan, called Project BioShield, and allocated $5.6 billion to develop vaccines and treatments.

The VaxGen anthrax vaccine is the biggest BioShield program by far, but it has been plagued by difficulties. VaxGen, in a conference call with analysts yesterday, said the government had "unilaterally" imposed burdensome new requirements. In particular, the company said the new rules require it to spend millions to complete an extra human test of the vaccine before the government will accept it into national stockpiles. VaxGen has run into quality-control problems with test lots of its vaccine, problems the company claims it is well on its way to fixing.

Health and Human Services, in its statement, emphasized that it was "committed to aggressively pursuing our biodefense mission."

Several stock analysts accepted VaxGen's interpretation of events yesterday -- and downgraded the company's shares. "We believe this news adds substantial additional risk to [the] anthrax program, both from cost and execution perspective, and delays meaningful" revenue to the company until 2009, analyst Bret Holley and colleagues at CIBC World Markets wrote in a bulletin to investors.

VaxGen, which lost millions of dollars working on an AIDS vaccine that failed, has had severe accounting, financial and management problems, many of them evident long before the government entrusted its biggest BioShield project to the company. The company has been thrown off regular stock exchanges because of accounting problems that prevent it from filing financial statements, and it trades in an over-the-counter market known as the pink sheets.

VaxGen share price fell by nearly half during midday trading yesterday but recovered at day's end to close at $4.99, down 37 percent.

U.S. Wants More Tests of VaxGen's Anthrax Vaccine

Financially struggling VaxGen Inc. said Wednesday that the federal government was demanding that the biotechnology company conduct more human tests before delivering a new anthrax vaccine.

The government made the costly requirements unilaterally and doesn't intend to cover the added cost, the Brisbane, Calif.-based company said.

The government will not pay VaxGen until it begins delivering the 75 million dosages ordered, which are now expected in 2008. It is the second delay since the company won the $877.5 million contract in 2004.

The government is VaxGen's only customer and its stock plummeted $2.96, or 37%, to $4.99.

"Financing an increased scope of work and delays imposed without compensation is the greatest challenge we have faced," said Lance Gordon, VaxGen's chief executive.

The contract was the first awarded under Project BioShield, a law President Bush signed in 2004 that promises $5.6 billion to develop remedies against bioweapons. The small biotechnology company has been trying to refashion itself as a biodefense specialist since its experimental AIDS vaccine flopped in 2003.

Gordon said the company had asked the Health and Human Services Department to reconsider its new demands and was "pursuing legal remedies" to recoup costs to test more people with the experimental vaccine.

Migrating Birds Didn't Carry Flu

The New York TimesBy ELISABETH ROSENTHAL

ROME, May 10 — Defying the dire predictions of health officials, the flocks of migratory birds that flew south to Africa last fall, then back over Europe in recent weeks did not carry the deadly bird flu virus or spread it during their annual journey, scientists have concluded.

International health officials had feared that the disease was likely to spread to Africa during the southward migration and return to Europe with a vengeance during the reverse migration this spring. That has not happened — a significant finding for Europe, because it is far easier to monitor a virus that exists domestically on farms but not in the wild. "It is quiet now in terms of cases, which is contrary to what many people had expected," said Ward Hagemeijer, a bird flu specialist with Wetlands International, an environmental group based in the Netherlands that studies migratory birds.

In thousands of samples collected in Africa this winter, the bird flu virus, A(H5N1), was not detected in a single wild bird, health officials and scientists said. In Europe, only a few cases have been detected in wild birds since April 1, at the height of the migration north.

The number of cases in Europe has fallen off so steeply compared with February, when dozens of new cases were found daily, that specialists contend that the northward spring migration played no role. The flu was found in one grebe in Denmark on April 28 — the last case discovered — and a falcon in Germany and a few swans in France, said the World Organization for Animal Health, based in Paris.

In response to the good news, agriculture officials in many European countries are lifting restrictions intended to protect valuable poultry from infected wild birds.

Last week, the Netherlands and Switzerland rescinded mandates that poultry be kept indoors. Austria has loosened similar regulations, and France is considering doing so. The cases in Europe in February were attributed to infected wild birds that traveled west to avoid severe cold in Russia and Central Asia but apparently never carried the virus to Africa. The international scientists who had issued the earlier warnings are perplexed, unsure if their precautions — like intensive surveillance and eliminating contact between poultry and wild birds — helped defuse a time bomb or if nature simply granted a reprieve.

"Is it like Y2K, where also nothing happened?" asked Juan Lubroth, a senior veterinary official at the United Nations Food and Agriculture Organization in Rome, referring to the expected computer failures that did not materialize as 1999 turned to 2000. "Perhaps it is because it was not as bad as we feared, or perhaps it is because people took the right measures."

Still, he and others say, the lack of wild bird cases in Europe only underscores how little is understood about the virus. And scientists warn that it could return to Europe.

"Maybe we will be lucky and this virus will just die out in the wild," Mr. Lubroth said. "But maybe it will come back strong next year. We just don't have the answers."

The feared A(H5N1) bird flu virus does not now spread among humans, although scientists are worried it may acquire that ability through natural processes, setting off a worldwide pandemic. The less bird flu is present in nature and domestically on farms, the less likely it is for such an evolution to occur, they say.

Worldwide, bird flu has killed about 200 humans, almost all of whom were in extremely close contact with sick birds.

Specialists from Wetlands International, who were deputized by the Food and Agriculture Organization, sampled 7,500 African wild birds last winter in a search for the disease. They found no A(H5N1), Mr. Hagemeijer said, so it is not surprising that it did not return to Europe with the spring migration.

While bird flu has become a huge problem in poultry on farms in a few African countries, including Egypt, Nigeria and Sudan, specialists increasingly suspect that it was introduced in those countries through imported infected poultry and poultry products. Mr. Hagemeijer said the strength of the virus among wild birds possibly weakened as the southward migration season progressed, a trait he said was common in less dangerous bird flu viruses. That probably limited its spread in Africa, he said.

A(H5N1) is the most deadly of a large family of bird flu viruses, most of which produce only minor illness in birds.

Many bird flu viruses are picked up by migratory birds in their nesting places in northern lakes during the summer and fall breeding season. As the months pass, the viruses show a decreasing pattern of spread and contamination.

"So it tends to be mostly a north-to-south spread, and then it wanes," Mr. Hagemeijer said.

Still, this means that the cycle could start again this summer, if the virus — which can live for long periods in water — has persisted in those breeding areas. Many bird specialists contend that a small number of wetland lakes in Central Asia and Russia may harbor the virus all the time, serving as the origin of European and Central Asian infections.

Scientists still do not know which birds carry the virus silently and which die from it quickly, or how it typically spreads from wild bird to wild bird, or between wild birds and poultry.

Farm-based outbreaks of bird flu still occur constantly in a number of countries, although not in Europe. Ivory Coast had its first outbreak of bird flu, on a farm, last week.

But other countries, like Turkey, have made substantial progress in containing the disease among poultry, Mr. Lubroth said. He added that he hoped that quick measures to limit outbreaks had reduced the virus's spread in Africa.

After the virus was found on farms in Nigeria in January, many specialists expected it to spread rapidly among farms and into wild birds in the region. Apparently, it did not.

"Why didn't it sweep up the coast from Niger, to Benin and Senegal and back up through Europe? Why didn't it hit Africa's big lakes?" Mr. Lubroth asked.

"All we have are a few snapshots of the virus. What we need is a movie of its life cycle."

May 10, 2006

Feds demand VaxGen conduct more anthrax vaccine tests

PAUL ELIASAssociated Press

SAN FRANCISCO - Struggling biotechnology company VaxGen Inc. said Wednesday that the federal government is demanding more human tests on a new anthrax vaccine, a costly requirement that imperils the company's existence and the $877.5 million government contract along with it.

The government ordered the additional tests "unilaterally," without formal negotiations and it doesn't intend to cover the extra costs, company executives said.

Further, the government will not pay VaxGen until it begins delivering the 75 million shots ordered under the 2004 contract.

The first shipments aren't expected until 2008 now and there's a concern the company will run out of money before then. The government is the company's only customer and VaxGen's will run out of cash by the end of the third quarter without new investments.

"This places a significant financial burden on the company," said VaxGen senior vice president James Panek, who runs the company's anthrax program. Company officials have called on government officials to rescind its new demands, but they said it appears VaxGen and the government are heading to court over the matter.

The contract was the first awarded under Project BioShield, a law President Bush signed in 2004 that promises $5.6 billion to develop remedies against bioweapons.

"The modification is an extension of time and effects no substantive changes to the contract work," said Noreen Hynes of the Department of Health and Human Services, which manages most Project Bioshield contracts. "Appropriate standards for demonstrating safety, efficacy, stability and manufacturing consistency were established in the November 2004 contract, and remain."

Hynes gave no reason for the delay and company officials said they didn't know why the government is demanding the new tests.

Troubles with the vaccine's potency last year caused an initial delivery delay, but company officials said Wednesday they were close to fixing those problems. Concerned analysts and investors fretted during a conference call with VaxGen officials Wednesday that the government was seeking to get out of the contract, a scenario company executives downplayed.

"We see this as a contract dispute rather than a deterioration of the overall working relationship," Panek sad.

The company's stock plummeted 37 percent to $4.99 a share at the close of trading Wednesday on the "Pink Sheets" electronic bulletin board. The Nasdaq Stock Market kicked the company off its exchange in 2004 for failing to file timely financial reports.

Vaxgen in March was also warned by the Food and Drug Administrations that sales material handed out at a government biodefense research meeting last year contained "false and misleading statements" about the experimental vaccine and how it compared to competitor, BioPort Corp. of Lansing, Mich.

Seiler also said that changing the terms of the contract without consulting VaxGen could dissuade other companies from doing business with the government.

"If the government keeps moving the goal posts, then I can't imagine why anyone would want to do business with it," Seiler said.

The small biotechnology company, based in Brisbane, Calif., has tried to refashion itself as a biodefense specialist since its experimental AIDS vaccine flopped in 2003.

The company's vaccine is made by genetically engineering small bits of the anthrax virus to provoke an immune response. The vaccine requires each person to take three shots rather than the six shots required by an older vaccine.